On 21 June 2006, the European Commission approved the sale of rimonabant in the then-25-member European Union as a prescription drug for use in conjunction with diet and exercise for patients with a body mass index (BMI) greater than 30 kg/m², or patients with a BMI greater than 27 kg/m² with associated risk factors, such as type 2 diabetes or dyslipidaemia.[7] It was first in its class to be approved anywhere in the world.[5]

Rimonabant was submitted to the Food and Drug Administration (FDA) for approval in the United States in 2005; in 2007, the FDA’s Endocrine and Metabolic Drugs Advisory Committee (EMDAC) concluded that Sanofi-Aventis failed to demonstrate the safety of rimonabant and voted against recommending the anti-obesity treatment for approval[8] and two weeks later the company withdrew the application.[9]

Data from clinical trials submitted to regulatory authorities showed that rimonabant caused depressive disorders or mood alterations in up to 10% of subjects and suicidal ideation in around 1%, and in Europe it was contraindicated for people with any psychiatric disorder, including depressed or suicidal individuals.[7]

Additionally, nausea and upper respiratory tract infections were very common (occurring in more than 10% of people) adverse effects; common adverse effects (occurring in between 1% and 10% of people) included gastroenteritis, anxiety, irritability, insomnia and other sleep disorders, hot flushes, diarrhea, vomiting, dry or itchy skin, tendonitis, muscle cramps and spasms, fatigue, flu-like symptoms, and increased risk of falling.

The FDA’s advisory committee raised concerns that based on animal data, it appeared that the therapeutic window with regard to CNS toxicity, and specifically seizures was almost nonexistent; the therapeutic dose and the dose that caused seizures in animals appeared to be the same.[2][14][15]

When the EMA reviewed postmarketing surveillance data, it found that the risk of psychiatric disorders in people taking rimonabant was doubled.[2]

Along with the clinical trials in obesity that generated the data submitted to regulatory authorities,[17] rimonabant was also studied in clinical trials as a potential treatment for other conditions,[2] including diabetes, atherosclerosis, and smoking cessation.[18][19]